Uterus: Low-grade endometrial stromal sarcoma with t(X;17)(p11.2;q21.33) MBTD1/CXorf6

Short communication on t(X;17)(p11.2;q21.33) MBTD1-CXorf67 in low-grade endometrial stromal sarcoma

Urinary bladder inflammatory myofibroblastic tumor with ALK-ATIC fusion

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Downstream and Intermediate Interactions of Synovial Sarcoma-Associated Fusion Oncoproteins and Their Implication for Targeted Therapy

Synovial sarcoma (SS), an aggressive type of soft tissue tumor, occurs mostly in adolescents and young adults. The origin and molecular mechanism of the development of SS remain only partially known. Over 90% of SS cases are characterized by the t(X;18)(p11.2;q11.2) translocation, which results mainly in the formation of SS18-SSX1 or SS18-SSX2 fusion genes. In recent years, several reports describing direct and indirect interactions of SS18-SSX1/SSX2 oncoproteins have been published. These reports suggest that the fusion proteins particularly affect the cell growth, cell proliferation, TP53 pathway, and chromatin remodeling mechanisms, contributing to SS oncogenesis. Additional research efforts are required to fully explore the protein-protein interactions of SS18-SSX oncoproteins and the pathways that are regulated by these partnerships for the development of effective targeted therapy

A Sarcoma at the Site of Previous Extravasation of Adriamycin

We report the case of a 66-year-old man presenting with a high-grade pleomorphic sarcoma at the left elbow 16 years after the extravasation of adriamycin given for a malignant ifbrous histiocytoma of the tibia.We suggest that this sarcoma originated in a multistep way over many years, out of the chronic inflammatory tissue that developed due to a non-specific cellular damage at the nuclear level, interfering with normal cell replication necessary for normal healing tissue healing. As a result, the non-healed chronic inflammatory tissue transformed over several years into a preneoplastic mesenchymal tumour and later into a high-grade pleomorphic sarcoma

Case report: Cardiac intimal sarcoma in a young child

Undifferentiated mesenchymal tumors from the intimal layer (intimal sarcomas) are rare within the ventricles and exceptional in children. A rare case of an intimal sarcoma located in the right ventricle in a young child is presented with need for urgent surgical resection due to mechanical flow obstruction. Tumor cells showed amplification of MDM2 gene and a homozygous loss of CDKN2A on 9p21. A review of the literature regarding primary cardiac malignancies and intimal sarcoma in children is provided

High-grade endometrial stromal sarcoma presenting in a 28-year-old woman during pregnancy: a case report

<p>Abstract</p> <p>Introduction</p> <p>To the best of our knowledge, soft tissue sarcomas have not prevously been reported as a complication during pregnancy.</p> <p>Case presentation</p> <p>A 28-year-old Caucasian woman was diagnosed with a transperitoneal sarcoma during pregnancy. Morphological, immunohistochemical, chromosomal and mutational analyses pointed towards a high-grade endometrial stromal sarcoma. Although surgery and chemotherapy are possible during pregnancy, we were unable to perform these in this case.</p> <p>Conclusion</p> <p>The potential to treat gynecological cancer during pregnancy should always be assessed individually.</p

Advanced or metastatic gastrointestinal stromal tumors: Systemic treatment options

Gastrointestinal stromal tumor (GIST), the most common sarcoma arising in the gastrointestinal tract, typically expresses the tyrosine‐kinase receptor, C‐KIT, and contains activating mutation in the c‐kit or platelet‐derived growth factor receptor ( pdgfr ) gene. Recently, development of small molecules that inhibit the kinase activity of mutant C‐KIT and PDGFR proteins has radically changed treatment and prognosis of patients diagnosed with advanced GIST as this molecularly “targeted” therapy has demonstrated remarkable high‐level of activity in this disease. J. Surg. Oncol. 2011; 104:888–895. © 2011 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88051/1/21930_ftp.pd

Post-Transcriptional Dysregulation by miRNAs Is Implicated in the Pathogenesis of Gastrointestinal Stromal Tumor [GIST]

peer-reviewedIn contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate posttranscriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wildtype gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly.Funding was obtained from the Medical Research Charities Group (http://www.mrcg.ie/) and Health Research Board of Ireland (http://www.hrb.ie) (MO’S), The Children’s Medical and Research Foundation (http://www.cmrf.org) (MO’S), the GIST Cancer Awareness Foundation [GCAF] (http://www. gistawareness.org/)(MO’S), and research grants from the Life Raft Group (http://www.liferaftgroup.org/)(MD-R) and from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (http://www.fwo.be/)(grant # G.0286.05 MD-R)